Prostate Cancer “Homing Device” Developed
A team of Purdue University researchers has synthesized a molecule that finds and penetrates prostate cancer cells and has created imaging agents and therapeutic drugs that can link to the molecule and be carried with it as cargo.

click to enlarge Transporter molecules carrying therapeutic drugs to PSMA targets in a prostate cancer cell.

Philip Low, team leader, said a targeted treatment could be much more effective in treating cancer and would greatly reduce the harmful side effects associated with current treatments. “By being able to target only the cancer cells, we could eliminate toxic side effects of treatments. In addition, the ability to target only the cancer cells can greatly improve imaging of the cancer to diagnose the disease, determine if it has spread or is responding to treatment.”

The molecule Low’s team created attaches to prostate-specific membrane antigen, or PSMA, a protein that is found on the membrane of more than 90 percent of all prostate cancers. It also is found on the blood vessels of most solid tumors and could provide a way to cut off the tumor blood supply, Low said.

“A lot of new drugs are being designed to destroy the vasculature of solid tumors, and, if they could be linked to this new targeting molecule, we could have a two-pronged attack for prostate cancer,” he said. “We could not only kill the prostate cancer cells directly, we could also destroy the vasculature that feeds the tumors.”

A radioimaging agent linked to the targeting molecule will be injected into prostate cancer patients and pictures will be taken using a special camera that detects radioactivity. The pictures show where the cancer is present to help doctors determine if it has metastasized, or spread, to any other areas of the body. It also will help doctors decide on the best course of treatment. There is currently only one radioimaging agent for prostate cancer approved by the FDA.

Researchers Assemble New Cancer Delivery System
University of Illinois researchers report that they have assembled a new cancer drug delivery system that manages to kill tumor cells while sparing healthy ones.

Attempts to direct liposomes to specific cancer cells, however, has met with limited success. A common approach involves attaching an antibody to the liposome membrane, but developing these antibodies is costly and time-consuming. Additionally, antibodies spur an immune response, requiring extra steps to create a useable therapeutic agent.

To solve the cell-targeting problem, the team turned to aptamers, short strands of DNA or RNA that are highly efficient binders, and are very easy to make, label, and manipulate.

click to enlarge Confocal images of selective targeting of breast cancer cells (top) but not prostate cancer cells (bottom). (Image: University of Illinois)

Lu’s laboratory specializes in isolating aptamers that bind to specific molecules and converting them into effective sensors and diagnostic agents. His team used an aptamer that binds to nucleolin receptors, which are found in abundance on certain breast cancer cells. The researchers then developed an effective method for attaching the aptamer to a liposome loaded with cisplatin, a drug that effectively kills cancer cells but has troublesome side effects when administered intravenously.
Tests in cells grown in the lab yielded promising results. Four days after they exposed the cells to the new drug-delivery system, 59.5% of the breast cancer cells had died, while less than 12% of breast cancer cells treated with cisplatin alone had died.

“By labeling a liposome that contains cisplatin with a cancer cell-specific aptamer, we have shown delivery of the drugs to cancer cells without significant damage to regular cells,” Lu said, “making it possible to maximize the drug potency while minimizing its side effects.”

This approach “integrates the advantages of small molecules and antibodies,” said Cheng, who helped pioneer the use of aptamers as targeting molecules for drug delivery. “This is the first study to integrate the aptamers and the liposome.”

Another advantage of using aptamers as targeting agents is that they are easily disabled. They readily bind to complementary DNA, which prevents them from interacting with cell receptors.
The new approach will be useful for many applications, Wong said. “What we’re really doing here is coming up with a general toolbox to deal with a broad range of cancers.”

“You can change aptamers to target a different type of cancer, you can change the therapeutic molecules to fight cancer or other diseases, and you can reverse the dose,” Cheng said. “That’s a lot of tools in the toolbox. It has great potential.”

Xelair Series 5 Automated Inhaler Tester
Leading automation developer, Astech Projects, has launched its new fully automated Xelair Series 5 system for automated inhaler testing. This system incorporates all existing features of the Xelair 1 and 3 series such as reduced variability, increased productivity and cost reduction. Additionally, the Xelair Series 5 includes the Device Handling and Storage (DHS) module with optional waste fire, which offers fully automated storage, handling and transfer of all devices. The need for manual inhaler firing is eliminated, enabling the user to leave the system to operate unattended for up to 24 hours.

Utilizing the latest robotic manipulator technology for increased throughput, robustness and flexibility, the Xelair Series 5 system offers an increased capacity for emitted dose collection. Furthermore, the ability to test up to 200 inhalers per day maximizes testing in the minimal amount of time. This technology provides a fully automated solution for testing dose content uniformity of the emitted dose, with each system and module designed to allow easy integration with each unique product.

University of Dundee to Lead Project to Deliver Cancer Treatments
The University of Dundee will lead a €2 million European Union-funded project to develop new methods of delivering cancer treatments.

The university will collaborate with international companies InSightec Ltd. and CapsuTech Ltd. on the NANOPORATION project, which will develop more efficient methods of delivering chemotherapy. These will integrate MRI, focused ultrasound, and potentially photonics, with the delivery and activation of nanocapsules carrying anti-cancer drugs to effectively target tumors.

“All of the established methods of cancer treatment have significant drawbacks, in that they cause side effects, require invasive procedures or do not deliver their therapeutic effect in an effective manner,” said Professor Andreas Melzer, Director of the Institute for Medical Science and Technology (IMSaT) at the University of Dundee.

“If we can combine these technologies of ultrasound, MRI, and nanocapsules, as well as microbubbles, we will be able to release proven anti-cancer drugs in high concentration only in the area where they are required.

“The project partners have existing technology in each of the areas we are looking at. What we need to do is combine the best of it to create a new system, which can deliver this very effective model of treatment.”

The treatment envisaged by the project leaders involves drugs being injected into the body in the form of tiny capsules, which are harmless until they are activated by a concentrated focused ultrasound “blast”, using devices developed in IMSaT’s medical ultrasound laboratories as well as commercial systems. The MRI scanner will be used to track the passage of the drugs, visualize the target and monitor the delivery of the drug treatment.

With the focused ultrasound concentrated on the exact position of the tumor in the body, damage to surrounding tissue is minimized and the effective delivery of the drug to the target cells is significantly increased.

“The aim with all cancer treatment is to target the specific area of the tumor and remove it while causing as little damage to surrounding tissue as possible, and reducing the side effects of drug treatments.”

IMSaT has multi-modality MRI, focused ultrasound, and other capabilities to deliver this kind of research. InSightec and CapsuTech deal with different aspects of targeted drug discovery. InSightec is a manufacturer and developer of unique MR-guided focused ultrasound systems and CapsuTech is a developer of a drug delivery platform based on targeted nanocapsules.

Circ and Elan Enter Development Agreement
Circ Pharma Limited and Elan Corporation plc have entered into a development agreement to develop a chronotherapeutic formulation of tramadol for the treatment of moderate to moderately severe pain.

The product incorporates Circ Pharma’s proprietary drug delivery technology enabling once daily dosing. Circ’s technology provides for minimized delivery to the body during sleeping hours, acceleration of drug absorption immediately prior to the waking hours and the subsequent maintenance of efficacious drug levels. Circ has successfully completed Phase 1 testing on the product. Currently the worldwide market for pain treatments is worth about $26 billion and is forecast to grow to about $31 billion by 2011. In the US and Europe the moderate to severe pain market was estimated to be worth about $6.7 billion in 2007. The US-Europe tramadol market was worth about $1.1 billion in 2008. Circ Pharma intends to seek a licensing partner for worldwide commercial distribution of the product.

The agreement provides that Elan support the continued formulation and manufacturing activities required to seek regulatory approval for this product in the US and elsewhere. “Elan’s extensive experience, know-how and technology for the development and manufacture of scheduled products for the US market will ensure that we can quickly and efficiently complete all the development and clinical activities required for Chrono Tramadol.” said Circ Pharma’s Chief Technical Officer, Margot Foynes.

MannKind Reveals Next-Generation Inhalation System
MannKind Corporation has begun clinical development of a next-generation inhalation system to optimize the delivery of drug powders based on the proprietary Technosphere technology platform. The inhalation system is as small as a whistle and designed to be easy-to-use, discreet, and patient-friendly when used with therapies such as the investigational ultrarapid-acting insulin AFRESA (insulin human [rDNA origin]) Inhalation Powder. The delivery system technology can also be used with other therapeutic proteins.

Hakan S. Edstrom, president and COO of MannKind said, “Our goals with this technology platform are to ... service the expanding market of patient self-administration.” MannKind’s proprietary Technosphere technology platform is based on a class of organic molecules that are designed to self-assemble into small particles onto which drug molecules can be loaded. The technology enables rapid systemic delivery of a broad range of therapeutic agents, including proteins, peptides and small molecule drugs, via oral inhalation to the deep lung.

NuSil Launches New Line of Silicone for Drug Delivery
NuSil Technology has launched the Drug Delivery Silicone (DDS) line of materials and services intended specifically for drug delivery and combination medical device products. For decades, NuSil Technology’s line of silicone fluids, elastomers, and gels have been used for drug delivery and medical devices—including matrix and reservoir-type delivery devices for transdermal, transmucousal, and long- and short-term implanted medical devices.

“We strive to meet the demands of the latest and most innovative drug delivery technologies by building upon our experience and expanding our products and services to offer one-of-a-kind support for our silicone materials,” said Brian Nash, NuSil Technology’s vice president of Marketing and Sales.

NuSil’s regulatory support for its products includes extensive physical, chemical and biological testing in the form of master access files (MAFs) submitted to the US Food and Drug Administration (FDA) for silicone materials intended for both short- and long-term implantable applications. NuSil has extended its level of regulatory support for the DDS materials by offering drug master files (DMFs) as well as testing guided by applicable European Pharmacopeia Monographs. Additional features include customized, certified per-lot testing. Unique lot numbers may also be assigned to each uncured silicone part to ensure that identification standards within the pharmaceutical industry are met.
 
Also, DDS materials can be customized for specific applications and tailored to influence the release of a wide range of active pharmaceutical ingredients (APIs). On a large or small scale, NuSil has the manufacturing capacity and capability to incorporate APIs directly into silicones in its production-scale manufacturing site.

Microtest Labs Adds Dissolution Testing Service
Microtest Laboratories, a leading single source provider of contract analytical solutions, is adding dissolution testing to its current suite of analytical testing and stability testing services.

Dissolution is a compendial method used to measure a drug’s rate of release from its dosage form. It is a complement to other analytical assays—potency and related substances (Microtest already offers both)—that characterize the dosage form. It can also be used to compare one dosage form to another or to estimate release and absorption rates in humans after an in vitro-in vivo correlation is established. “The addition of dissolution testing is the perfect complement to our portfolio of services,” said Steven Richter, PhD, president and scientific founder of Microtest Laboratories. “By offering an even more comprehensive array of assays, we’re increasing the convenience, efficiency, and value that we deliver as a single, preferred provider of contract laboratory services."